CHAPTER 11: Membrane Interactions of Amphiphilic Peptides with Antimicrobial Potential: A Solid-State NMR Study
Published:24 Feb 2014
M. Fillion, N. Voyer, and M. Auger, in Advances in Biological Solid-State NMR: Proteins and Membrane-Active Peptides, ed. F. Separovic and A. Naito, The Royal Society of Chemistry, 2014, pp. 200-213.
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A wide variety of organisms produce antimicrobial peptides as part of their first line of defence. These short cationic peptides are being considered as a new generation of antibiotics and represent great hopes against multiresistant bacteria which constitute an important clinical problem. We have investigated a non-natural peptide composed of 14 residues (10 leucines and 4 phenylalanines modified with a crown ether), the so-called base 14-mer peptide. The results indicate that the peptide sits at the surface of the membrane and perturbs the local orientation of the phospholipids, resulting in the formation of transient pores. To gain specificity against negatively charged membranes, positively charged lysine residues were substituted for several leucines of this 14-mer peptide. All peptides have been shown to induce significant calcein leakage of anionic vesicles, but some peptides do not induce significant leakage of zwitterionic vesicles and are thus only active against bacterial model membranes. 2H NMR results indicate that leakage of vesicles induced by 14-mer peptides is accompanied by an increase of the order of the lipid acyl chains. Thus leakage from vesicles is due to pore formation rather than membrane micellization by these peptides.